As a cornerstone of the Merck approach to the development of companion diagnostics (CDx), we have developed a CDx guide that is applied across the company to all drug discovery projects. The CDx guide ensures that every project includes a CDx strategy that is fit for purpose and compliant with regulatory requirements. To this end, the CDx guide is built upon the key regulatory CDx documents provided by the US Food and Drug Administration and the Council of the European Union. The guide poses critical questions at each stage of the pipeline, and provides access to the resources needed to address these questions. This approach allows teams to develop innovative CDx strategies with the benefit of expert guidance.